Peers Chris, Smith Ian F, Boyle John P, Pearson Hugh A
School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
Biol Chem. 2004 Mar-Apr;385(3-4):285-9. doi: 10.1515/BC.2004.023.
Sustained central hypoxia predisposes individuals to dementias such as Alzheimer's disease, in which cells are destroyed in part by disruption of Ca2+ homeostasis. Here, we show that exposure of astrocytes to hypoxia in vitro causes inhibition of plasmalemmal Na+/Ca2+ exchange and excessive mitochondrial Ca2+ loading. Both factors disrupt normal agonist-evoked Ca2+ signalling. Moreover, hypoxia increases the levels of presenilin-1, a major component of a key enzyme involved in Alzheimer's disease. Inhibition of this enzyme partially reverses the effects of hypoxia on Ca2+ signalling. These findings provide an initial cellular basis for understanding the clinical association of hypoxia with Alzheimer's disease.
持续性中枢性缺氧使个体易患诸如阿尔茨海默病之类的痴呆症，在这类疾病中，细胞部分是因钙离子稳态的破坏而被摧毁。在此，我们表明，体外培养的星形胶质细胞暴露于缺氧环境会导致质膜钠/钙交换受抑制以及线粒体钙过度负载。这两个因素都会扰乱正常的激动剂诱发的钙信号传导。此外，缺氧会增加早老素-1的水平，早老素-1是参与阿尔茨海默病的一种关键酶的主要成分。抑制这种酶可部分逆转缺氧对钙信号传导的影响。这些发现为理解缺氧与阿尔茨海默病的临床关联提供了初步的细胞基础。
